In still-young individuals, increasing these myokines may be a compensatory response to improve insulin sensitivity in obesity or the consequence of reduced sensitivity to its effects, as seen with insulin and leptin in obesity.49,50 Upregulated IL-6 and GDF-15 have also been used to feature cell senescence in vitro, particularly in the senescence-associated secretory phenotype.51 This evidence concerns the gene GDF15 and obesity due to melanocortin 4 receptor deficiency.